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Electrical conductivity is a pivotal biophysical factor for neural interfaces, though optimal values remain controversial due to challenges isolating this cue. To address this issue, conductive substrates made of carbon nanotubes and graphene oxide nanoribbons, exhibiting a spectrum of conductivities from 0.02 to 3.2 S m-1, while controlling other surface properties is designed. The focus is to ascertain whether varying conductivity in isolation has any discernable impact on neural lineage specification. Remarkably, neural-tissue-like low conductivity (0.02-0.1 S m-1) prompted neural stem/progenitor cells to exhibit a greater propensity toward neuronal lineage specification (neurons and oligodendrocytes, not astrocytes) compared to high supraphysiological conductivity (3.2 S m-1). High conductivity instigated the apoptotic process, characterized by increased apoptotic fraction and decreased neurogenic morphological features, primarily due to calcium overload. Conversely, cells exposed to physiological conductivity displayed epigenetic changes, specifically increased chromatin openness with H3acetylation (H3ac) and neurogenic-transcription-factor activation, along with a more balanced intracellular calcium response. The pharmacological inhibition of H3ac further supported the idea that such epigenetic changes might play a key role in driving neuronal specification in response to neural-tissue-like, not supraphysiological, conductive cues. These findings underscore the necessity of optimal conductivity when designing neural interfaces and scaffolds to stimulate neuronal differentiation and facilitate the repair process.
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OBJECTIVE: To investigate the relationship between mutated genes and clinical features in patients with essential thrombocythemia (ET). METHODS: The clinical data of 69 patients with ET from October 2018 to March 2022 were retrospectively analyzed. According to driver mutation type, patients were divided into JAK2 group, CALR group and triple-negative group. The sex, age, cardiovascular risk factors, thrombosis, splenomegaly, routine blood test and coagulation status of patients in three groups were analyzed. RESULTS: Among 69 ET patients, 46 cases were associated with JAK2 mutation, 14 cases with CALR mutation, 8 cases with triple-negative mutation, and one with MPL gene mutation. There were no significant differences in age and sex among the three groups (P >0.05). The highest thrombotic rate was 26.09% (12/46) in JAK2 group, then 12.5% (1/8) in triple-negative group, while no thrombotic events occurred in CALR group. The incidence of splenomegaly was the highest in JAK2 group (34.78%), while no splenomegaly occurred in triple-negative group. The white blood cell (WBC) count in JAK2 group was (9.00±4.86)×109/L, which was significantly higher than (6.03±2.32)×109/L in CALR group (P <0.05). The hemoglobin (Hb) and hematocrit (HCT) in JAK2 group were (148.42±18.79) g/L and (0.44±0.06)%, respectively, which were both significantly higher than (131.00±15.17) g/L and (0.39±0.05)% in triple-negative group (P <0.05). The platelet (PLT) in JAK2 group was (584.17±175.77)×109/L, which was significantly lower than (703.07±225.60)×109/L in CALR group (P <0.05). The fibrinogen (Fg) in JAK2 and triple-negative group were (2.64±0.69) g/L and (3.05±0.77) g/L, respectively, which were both significantly higher than (2.24±0.47) g/L in CALR group (P <0.05, P <0.01). The activated partial thromboplastin time (APTT) in triple-negative group was (28.61±1.99) s, which was significantly decreased compared with (31.45±3.35) s in CALR group (P <0.05). CONCLUSIONS: There are differences in blood cell count and coagulation status among ET patients with different driver gene mutations. Among ET patients, JAK2 mutation is most common. Compared with CALR group, the thrombotic rate, WBC and Fg significantly increase in JAK2 group, while PLT decrease. Compared with triple-negative group, the incidence of splenomegaly and HCT significantly increase. Compared with CALR group, Fg significantly increases but APTT decreases in triple-negative group.
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Trombocitemia Essencial , Trombose , Humanos , Calreticulina/genética , Janus Quinase 2/genética , Mutação , Estudos Retrospectivos , Esplenomegalia/complicações , Trombocitemia Essencial/genética , Trombocitemia Essencial/complicaçõesRESUMO
Combinations of different biomaterials with their own advantages as well as functionalization with other components have long been implemented in tissue engineering to improve the performance of the overall material. Biomaterials, particularly hydrogel platforms, have shown great potential for delivering compounds such as drugs, growth factors, and neurotrophic factors, as well as cells, in neural tissue engineering applications. In central the nervous system, astrocyte reactivity and glial scar formation are significant and complex challenges to tackle for neural and functional recovery. GelMA hydrogel-based tissue constructs have been developed in this study and combined with two different formulations of phosphate glass fibers (PGFs) (with Fe3+ or Ti2+ oxide) to impose physical and mechanical cues for modulating astrocyte cell behavior. This study was also aimed at investigating the effects of lithium-loaded GelMA-PGFs hydrogels in alleviating astrocyte reactivity and glial scar formation offering novel perspectives for neural tissue engineering applications. The rationale behind introducing lithium is driven by its long-proven therapeutic benefits in mental disorders, and neuroprotective and pronounced anti-inflammatory properties. The optimal concentrations of lithium and LPS were determined in vitro on primary rat astrocytes. Furthermore, qPCR was conducted for gene expression analysis of GFAP and IL-6 markers on primary astrocytes cultured 3D into GelMA and GelMA-PGFs hydrogels with and without lithium and in vitro stimulated with LPS for astrocyte reactivity. The results suggest that the combination of bioactive phosphate-based glass fibers and lithium loading into GelMA structures may impact GFAP expression and early IL-6 expression. Furthermore, GelMA-PGFs (Fe) constructs have shown improved performance in modulating glial scarring over GFAP regulation.
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Astrócitos , Vidro , Lítio , Fosfatos , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Animais , Vidro/química , Fosfatos/química , Fosfatos/farmacologia , Lítio/farmacologia , Lítio/química , Ratos , Hidrogéis/química , Hidrogéis/farmacologia , Alicerces Teciduais/química , Células Cultivadas , Proteína Glial Fibrilar Ácida/metabolismoRESUMO
OBJECTIVE: To understand the biological characteristics of polycythemia vera (PV) patients with myeloid fibroplasia, and further analyze the risk factors affecting myeloid fibroplasia in PV patients, so as to provide ideas for predicting the occurrence of myeloid fibroplasia in PV patients. METHODS: Forty patients with PV in the Department of Hematology, Xiyuan Hospital of China Academy of Chinese Medical Sciences were collected and divided into two groups, with (hyperplasia group) and without (Non-proliferative group) hyperplasia of bone marrow fibers. The differences of basic clinical characteristics, blood routine, biochemistry, bone marrow cells, coagulation function and other indicators between the two groups were compared, and the independent risk factors affecting the proliferation of bone marrow fibrous tissue in PV patients were further analyzed by multivariate regression. RESULTS: Compared with Non-proliferative group, the JAK2 mutation rate (95% vs 70%ï¼P=0.037), eosinophilic cell count (0.19 vs 0.11, P=0.047) and eosinophilic percentage (1.84 vs 1.27, P=0.001) in PV patients with hyperplasia were significantly increased, triglycerides (1.55 vs 1.91, P=0.038) and low-density lipoprotein (1.50 vs 3.08, P=0.000) were significantly reduced, bone marrow hematopoietic volume (0.85 vs 0.6, P=0.001), granulocyte/erythrocyte ratio (3.40 vs 1.89, P=0.033), lymphocyte/erythrocyte ratio (0.60 vs 0.42, P=0.033), and granulocyte+lymphocyte/erythrocyte ratio (3.72 vs 2.37, P=0.026) were significantly increased, thrombin time (18.84 vs 18.12, P=0.043) was significantly prolonged. Multivariate regression analysis results showed that peripheral blood eosinophil ≥2% and low-density lipoprotein ≤2 mmol/L were independent risk factors for bone marrow fibrous tissue hyperplasia in PV patients (P<0.05). CONCLUSION: Increased proportion of peripheral blood eosinophils and decreased low density lipoprotein are risk factors for bone marrow fibrous tissue hyperplasia in PV patients.
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Policitemia Vera , Policitemia , Humanos , Medula Óssea/patologia , Hiperplasia/patologia , Granulócitos/patologia , Janus Quinase 2/genética , Fatores de Risco , Lipoproteínas LDL , Policitemia/patologiaRESUMO
Introduction: Clonal integration of connected ramets within clones is an important ecological advantage. In this study, we tested the hypothesis that the effects of clonal integration on performance of donor and recipient ramets when one resource is heterogeneous can be influenced by the availability of another resource of donor ramets. Methods: We conducted a greenhouse experiment on the widespread, perennial herb Glechoma longituba. Clonal fragments consisting of pairs of connected ramets were grown for seven weeks. The younger, apical ramets were exposed under 30% or 100% light condition and the older, basal ramets were treated with three levels of nutrients. The connections between ramets were either severed or left intact. 30% light condition negatively affected the growth of apical ramets, basal ramets and the whole fragments. Results: Clonal integration significantly increased the growth of apical ramets, but decreased the growth of the basal ramets. Medium and high level nutrient availability of basal ramets significantly increased the growth of apical ramets, basal ramets and the whole fragments. At the high nutrient level, the reduction in growth of basal ramets from clonal integration was decreased, but the growth responses of apical ramets and the whole fragments to clonal integration were not influenced by nutrient availability. Conclusion: The results suggested that clonal integration was benefit to the growth of apical ramets of Glechoma longituba but at the cost of reducing the growth of basal ramets. Although the high nutrient level could reduce the cost that clonal integration brought to the unshaded basal ramets, but could not increase the benefit that clonal integration brought to the shaded apical ramets and whole fragment.
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Neural stem cells (NSC) have tremendous potential for therapeutic regeneration of diseased or traumatized neural tissues, including injured spinal cord. However, transplanted NSC suffer from low cell survival and uncontrolled differentiation, limiting in vivo efficacy. Here, this issue is tackled by delivery through silk-collagen protein hydrogels that are stiffness-matched, stress-relaxing, and shear-thinning. The mechanically-tuned hydrogels protect NSC reprogrammed from fibroblasts (iNSC) initially from injection shear-stress, and enhance long-term survival over 12 weeks. Hydrogel-iNSC treatment alleviates neural inflammation, with reduced inflammatory cells and lesions than NSC-only. The iNSC migrate from the hydrogel into surrounding tissues, secrete up-regulated neurotrophic factors, and differentiate into neural cell subtypes, forming synapses. More serotonergic axons are observed in the lesion cavity, and locomotor functions are improved in hydrogel-iNSC than in iNSC-only. This study highlights the ability of mechanically-tuned protein hydrogels to protect iNSC from the injection stress and severe inflammatory environment, allowing them to differentiate and function to recover the injured spinal cord.
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Células-Tronco Neurais , Traumatismos da Medula Espinal , Ratos , Animais , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/patologia , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Seda/metabolismo , Medula Espinal/patologia , Colágeno/metabolismo , Recuperação de Função FisiológicaRESUMO
Histone H3 lysine 4 (H3K4) methyltransferase 2D (KMT2D) plays an important role in cell development in early life. However, the function of KMT2D in adult cells such as cardiomyocytes or neurons has not been reported. In this study, cardiomyocyte-specific KMT2D knockout (KMT2D-cKO) and control (KMT2D-Ctl) mice were exposed to sham or myocardial ischemia (MI) surgery. Depletion of KMT2D aggravated the ischemic area, led to the increased mortality (26.5% in KMT2D-cKO vs 12.5% in KMT2D-Ctl) of the mice, and weakened the left ventricular systolic function. RNA-seq analysis in cardiac tissues identified genes whose expression was changed by MI and KMT2D deletion. Combined with the genome-wide association study (GWAS) analysis, cardiac disease-associated genes Rasd1, Thsd7a, Ednra, and Tns1 were identified. The expression of the Rasd1 was significantly decreased by MI or the loss of KMT2D in vivo. Meanwhile, ChIP assays demonstrated that either MI or loss of KMT2D attenuated monomethylated H3K4 (H3K4me1) enrichment on the enhancer of Rasd1. By generating a KMT2D knockout (H9C2-KO) H9C2 monoclone, we verified that the expression of Rasd1 was controlled by KMT2D, and the expression of Rasd1 was decreased by serum starvation but not low-(O2) treatment in H9C2 cells. KMT2D has a protective effect on ischemic myocardium by regulating cardiac disease-associated genes including Rasd1. KMT2D is required for the H3K4me1 deposition on the enhancer of Rasd1. Our data for the first time suggest that KMT2D-mediated Rasd1 expression may play an important protective effect on adult cells during nutritional deficiency caused by ischemic injury.
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IRON-REGULATED TRANSPORTER 1 (IRT1) is critical for iron uptake in roots, and its exocytosis to the plasma membrane (PM) is regulated by the iron status sensed by the histidine-rich domain (HRM). However, studies on the fate of IRT1 after fusion with PM in response to iron conditions are still limited. In this study, we found that K165 and K196 regulate the monoubiquitination of MxIRT1 (mUb-MxIRT1), which acts as a receptor delivering signals from HRM to downstream effectors such as clathrin to determine the fate of MxIRT1. Iron supply led MxIRT1 in the PM to monoubiquitin-dependent endocytosis which could be inhibited by endocytosis inhibitor TyrA23 or in the double site-directed mutant K165/K196R. Subsequently, the endocytosis pathway to the vacuole was inhibited by vacuolar protease inhibitor Leupeptin in excessive iron conditions and the inability of being able to respond to iron change, indicated by the protein accumulating in the PM, contributed to iron toxicity in K165/K196R transgenic Arabidopsis. With iron availability decreasing again, MxIRT1 could dock close to the PM waiting for to be recycled. Another monoubiquitination site, K26, was necessary for MxIRT1 Endoplasmic Reticulum (ER) export as site-directed mutant K26R lost the ability of PM targeting, and co-localized with the COPII subunit of the coat protein OsSec24. Therefore, after K26-directed ER export and iron-induced PM fusion, mUb-MxIRT1 determines subsequent vacuolar degradation or recycling to the PM via endocytosis for maintaining iron homeostasis.
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Arabidopsis , Vacúolos , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Transporte/metabolismo , Membrana Celular/metabolismo , Endocitose , Ubiquitinação , Vacúolos/metabolismoRESUMO
Histone methylation is one of the key post-translational modifications that plays a critical role in various heart diseases, including diabetic cardiomyopathy. A great deal of evidence has shown that histone methylation is closely related to hyperglycemia, insulin resistance, lipid and advanced glycation end products deposition, inflammatory and oxidative stress, endoplasmic reticulum stress and cell apoptosis, and these pathological factors play an important role in the pathogenesis of diabetic cardiomyopathy. In order to provide a novel theoretical basis and potential targets for the treatment of diabetic cardiomyopathy from the perspective of epigenetics, this review discussed and elucidated the association between histone methylation and the pathogenesis of diabetic cardiomyopathy in details.
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Diabetes Mellitus , Cardiomiopatias Diabéticas , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/patologia , Histonas , Humanos , Metilação , Estresse Oxidativo , Processamento de Proteína Pós-TraducionalRESUMO
BACKGROUND: Acupuncture at Neiguan (PC6) has long been used for treating cardiovascular diseases, but its antiarrhythmic effect and the underlying mechanisms have not yet been well investigated, especially regarding premature ventricular complexes (PVCs) that occur post-myocardial infarction (MI). The purpose of this study was to study the antiarrhythmic effect of manual acupuncture applied to PC6 for a relatively long period (28 days) and to elucidate the mechanism in mice. METHODS: An MI mouse model was generated by ligating the left anterior descending coronary artery in male C57/BL6 mice (n = 31). Manual acupuncture at PC6 was applied seven times weekly for 4 weeks. The state of myocardial injury was characterized by electrocardiography (ECG) and echocardiography. Inflammation was detected by ELISA and immunohistochemical stanning. Fibrosis was evaluated by Masson's trichrome staining. RNA sequencing was used to explore the differentially expressed genes (DEGs) among the different groups after treatment. RESULTS: Acupuncture at PC6 lowered the incidence of spontaneous PVCs after MI injury (1/9, 11%) compared to that in mice without acupuncture treatment (6/9, 67%) and improved the ejection fraction from 31.77% in the MI mice to 44.18% in the MI + PC6 mice. Fibrosis was reduced after PC6 treatment. RNA-seq showed many DEGs involved in the immune system and inflammatory response pathway. Further studies confirmed that inflammation at the circulation level and cardiac tissue was inhibited in MI + PC6 mice, accompanied by suppressed sympathetic activation. CONCLUSIONS: In conclusion, 28-day treatment of acupuncture at PC6 reduced spontaneous PVCs and improved systolic function, possibly by suppressing inflammatory response-mediated fibrosis and sympathetic hyperactivity.
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AbstractObjective: To analyze the DNA methylation gene mutations of myeloproliferative neoplasm (MPN), and preliminarily explore its clinical features. METHODS: Next-generation sequencing technology was used to detect 31 MPN-related genes in 105 cases of MPN patients ï¼»40 cases of polycythaemia vera (PV), 65 cases of essential thrombocythemia (ET)ï¼½, and to analyze the relationship between DNA methylation gene mutations and clinical features. RESULTS: 15 mutation types were detected in 105 patients (88 mutations in total), and the total mutation detection rate was 87.6% (92/105). A total of 23 mutations in 4 DNA methylation genes (TET2, DNMT3A, IDH1, IDH2) were detected in 22 patients. The mutation rate of DNA methylation genes was 21.0%, mainly in the form of double mutations, including JAK2 V617F and TET2 (n=10), JAK2 V617F and DNMT3A (n=4), CALR and TET2 (n=2), JAK2 V617F and IDH1 (n=1). Compared with MPN patients without DNA methylation gene mutations, the proportion of women with DNA methylation gene mutations and the white blood cell count (WBC) were significantly higher (P<0.05). Compared with MPN patients with triple-negative driver genes, the proportion of women with DNA methylation gene mutations, age, WBC, platelet count (PLT), and neutrophil-to-lymphocyte ratio (NLR) were significantly higher (P<0.05). The remaining difference was not statistically significant (P>0.05). The MPN10 score, the incidence of thrombotic events, and the proportion of medium-risk and high-risk patients with DNA methylation gene mutations were significantly higher than those of MPN patients without DNA methylation gene mutations (P<0.05). CONCLUSION: The mutation rate of DNA methylation genes was 21.0%, mainly coexisting in the form of double mutations. The proportion of women with DNA methylation gene mutations in MPN patients and WBC is high, the symptom load is heavy, the incidence of thrombosis is high, and the proportion of medium-high-risk patients is high, suggesting that their prognosis may be poor.
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Transtornos Mieloproliferativos , Policitemia Vera , Calreticulina/genética , Metilação de DNA , Feminino , Humanos , Janus Quinase 2/genética , Mutação , Transtornos Mieloproliferativos/genética , Policitemia Vera/genéticaRESUMO
The IRON-REGULATED TRANSPORTER1 (IRT1) is critical for iron uptake in roots, and its exocytosis to the plasma membrane (PM) is regulated by detergent-resistant membranes. However, studies on IRT1 exocytosis and function in response to iron status are limited. Presently, we found that the histidine-rich motif (HRM) of MxIRT1 could bind to iron directly and HRM determined the delivery of MxIRT1 to the PM, after which the cholesterol recognition amino acid consensus (CRAC) motif-regulated MxIRT1 mediated metal transport. IMAC assay revealed that H192 was the vital site for HRM binding to Fe2+, and metal-binding activity was stopped after the deletion of HRM (MxIRT1∆HM) or in H192 site-directed mutants (H192A). MxIRT1∆HM or H192A in transgenic yeast and Arabidopsis failed to localize in the PM and displayed impaired iron absorption. In the PM, Y266 in CRAC was required for metal transport; Y266A transgenic Arabidopsis displayed the same root length, Cd2+ flux, and Fe concentration as Arabidopsis mutant irt1 under iron-deficient conditions. Therefore, H192 in HRM may be an iron sensor to regulate delivery of MxIRT1 vesicles to the PM after binding with iron; Y266 in CRAC acts as an iron sensor for active metal transport under iron-deficient conditions.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Transporte de Cátions , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Transporte de Cátions/genética , Regulação da Expressão Gênica de Plantas , Histidina/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/metabolismoRESUMO
OBJECTIVE: Primary biliary cholangitis (PBC) is a progressive, autoimmune, cholestatic liver disease affecting approximately 15 000 individuals in the UK. Updated guidelines for the management of PBC were published by The European Association for the Study of the Liver (EASL) in 2017. We report on the first national, pilot audit that assesses the quality of care and adherence to guidelines. DESIGN: Data were collected from 11 National Health Service hospitals in England, Wales and Scotland between 2017 and 2020. Data on patient demographics, ursodeoxycholic acid (UDCA) dosing and key guideline recommendations were captured from medical records. Results from each hospital were evaluated for target achievement and underwent χ2 analysis for variation in performance between trusts. RESULTS: 790 patients' medical records were reviewed. The data demonstrated that the majority of hospitals did not meet all of the recommended EASL standards. Standards with the lowest likelihood of being met were identified as optimal UDCA dosing, assessment of bone density and assessment of clinical symptoms (pruritus and fatigue). Significant variations in meeting these three standards were observed across UK, in addition to assessment of biochemical response to UDCA (all p<0.0001) and assessment of transplant eligibility in high-risk patients (p=0.0297). CONCLUSION: Our findings identify a broad-based deficiency in 'real-world' PBC care, suggesting the need for an intervention to improve guideline adherence, ultimately improving patient outcomes. We developed the PBC Review tool and recommend its incorporation into clinical practice. As the first audit of its kind, it will be used to inform a future wide-scale reaudit.
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Stem cell therapy is one of the novel and prospective fields. The ability of stem cells to differentiate into different lineages makes them attractive candidates for several therapies. It is essential to understand the cell fate, distribution, and function of transplanted cells in the local microenvironment before their applications. Therefore, it is necessary to develop an accurate and reliable labeling method of stem cells for imaging techniques to track their translocation after transplantation. The graphitic quantum dots (GQDs) are selected among various stem cell labeling and tracking strategies which have high photoluminescence ability, photostability, relatively low cytotoxicity, tunable surface functional groups, and delivering capacity. Since GQDs interact easily with the cell and interfere with cell behavior through surface functional groups, an appropriate surface modification needs to be considered to get close to the ideal labeling nanoprobes. In this study, polyethylene glycol (PEG) is used to improve biocompatibility while simultaneously maintaining the photoluminescent potentials of GQDs. The biochemically inert PEG successfully covered the surface of GQDs. The PEG-GQDs composites show adequate bioimaging capabilities when internalized into neural stem/progenitor cells (NSPCs). Furthermore, the bio-inertness of the PEG-GQDs is confirmed. Herein, we introduce the PEG-GQDs as a valuable tool for stem cell labeling and tracking for biomedical therapies in the field of neural regeneration.
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Colorectal cancer (CRC) is a common malignant tumor of digestive system. CRC with micropapillary pattern (MPP) is an aggressive variant of colorectal adenocarcinoma. The aim of the present study was to clarify the clinicopathological significance and the prognostic role of an immunohistochemical marker, MPP, in CRC. The association between MPP and clinicopathological characteristics and prognosis in 286 cases of CRC (286/453 cases had follow-up information) were analysed. Then, 81 tissues without MPP and 90 tissues with MPP were analysed by immunohistochemistry using antibodies against villin, E-cadherin and epithelial membrane antigen (EMA). Bioinformatics was used to evaluate the expression of these three indicators in CRC. The proportion of micropapillary carcinoma in the overall tumour was ≥5%, and was observed in 90/453 cases (19.8%). The present data showed that CRC with MPP displayed higher rates of vascular and lymphatic invasion, a higher metastatic lymph node ratio and a higher pathological tumour and metastasis stage compared with CRC without MPP. The positive expression rates of EMA, E-cadherin and villin were 50.3, 93.4 and 96.5%, respectively. In 90 CRC cases with MPP, EMA inside-out pattern (I/OP) staining was observed in 26 cases (28.9%), and it was often focal and partial, while 37 cases (41.1%) had E-cadherin focal and partial staining compatible with reverse polarity. Villin I/OP staining was observed in 77 cases (85.6%), and circumferential staining predominated over partial staining. Overall, the data suggested that the presence of MPP is significantly associated with aggressive tumour behaviour and worse overall survival rate in CRC. Visualization and distinction of reverse polarity of colorectal micropapillary carcinomas is improved villin compared with EMA or E-cadherin.
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Abnormal autophagy is related to the pathogenesis and clinical symptoms of myelodysplastic syndrome (MDS). However, the effect of autophagy-related genes (ARGs) on the prognosis of MDS remains unclear. Here, we examined the expression profile of 108 patients with MDS from the GSE58831 dataset, and identified 22 genes that were significantly associated with overall survival. Among them, seven ARGs were screened and APIs were calculated for all samples based on the expression of the seven ARGs, and then, MDS patients were categorized into high- and low-risk groups based on the median APIs. The overall survival of patients with high-risk scores based on these seven ARGs was shorter than patients with low-risk scores in both the training cohort (P = 2.851e-06) and the validation cohort (P = 9.265e-03). Additionally, API showed an independent prognostic indicator for survival in the training samples [hazard ratio (HR) = 1.322, 95% confidence interval (CI): 1.158-1.51; P < 0.001] and the validation cohort (HR = 1.05, 95% CI: 1-1.1; P < 0.01). The area under the receiver operating characteristic curve (AUROC) of API and IPSS were 43.0137 and 66.0274 in the training cohorts and the AUC of the validation cohorts were 41.5361 and 72.0219. Our data indicate these seven ARGs can predict prognosis in patients with MDS and could guide individualized treatment.
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PURPOSE: The aims of this study were to examine (a) the effects of parental phubbing on teenagers' mobile phone dependency and (b) the mediating roles of subjective norm and dependent intention of underlying this relationship. METHODS: We recruited 605 middle school students in Beijing, China and they completed the parental phubbing behaviors, subjective norm, dependency intention, and mobile phone dependency behavior questionnaires. RESULTS: The results of the structure equation modeling revealed that parental phubbing behaviors significantly increased teenager's mobile phone dependency behaviors in two indirect ways. First, parental phubbing reinforced teenagers' mobile phone dependency intention, which in turn increased the likelihood of mobile phone dependency. Second, parental phubbing enhanced the tendency of parental mobile phone dependence norm perceived by teenagers, and thus reinforced their mobile phone dependency intention, ultimately increasing mobile phone dependency. CONCLUSION: We concluded that parental phubbing is a significant indicator of teenager mobile phone dependency and that mobile phone dependency intention plays a mediation role between them. In addition, the perceived parental mobile phone dependency norm played a mediation role between parental phubbing and mobile phone dependency intention and indirectly influenced the level of mobile phone dependency behaviors through the mediation effect of mobile phone dependency intention.
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OBJECTIVE: To assess the effect of storage time and temperature on complete blood count (CBC) and comprehensive metabolic panel (CMP) testing. METHODS: PubMed, EMBASE, the Cochrane Library of Systematic Reviews, Web of Science (WOS), China National Knowledge Infrastructure (CNKI), WanFang databases and SinoMed databases were searched up to May 2017. Clinical trials with adult whole blood samples were identified. Paired reviewers independently screened, extracted data and evaluated the quality of evidence (MINORS tool). Analyses were conducted using Revman 5.3 and Stata 14.0. RESULTS: A total of 89 studies were confirmed. For CBC, except MPV, most parameters were stable at least for 24h. Some indices, such as WBC, PLt, HCT, HGB and MCH were stable up to 3 d. However, stable CMP test results could only be acquired within 12h. at 4°C, including GLU, AST, ALT, Na, ALB, Cl, DBIL, TC, TG and ALP. Values were less stable when stored at RT. CONCLUSIONS: Specimens stored >12h. for CMP may generate unreliable results. For CBC, samples could reliably be stored for 24h. For longer storage, refrigeration (at 4°C) would be a better choice.